2025-08-06 早稲田大学
<関連情報>
ATRXの相分離凝集体が神経前駆細胞のアイデンティティを調節する Phase separated condensates of ATRX regulate neural progenitor identity
Ryo Tomooka,Tsukasa Sanosaka,Tamami Miyagi,Tomoko Andoh-Noda,Satoe Banno,Noriko Mizota,Kohsuke Kanekura,Hideyuki Okano & Jun Kohyama
Nature Communications Published:14 July 2025
DOI:https://doi.org/10.1038/s41467-025-61881-0
Abstract
Mutations in the ATRX genes cause alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome. Here, we show that ATRX influences the fate of human neural progenitor cells (hNPCs) by forming condensates through liquid-liquid phase separation (LLPS). The intrinsically disordered region (IDR) of ATRX is essential for LLPS and enables ATRX to form dynamic condensates that recruit co-activators. These condensates are necessary for ATRX localization at super-enhancers (SEs) in hNPCs, linking its compartmentalization to transcriptional regulation. Disruption of ATRX condensates alters gene expression and impairs neuronal differentiation. Our findings support a model in which ATRX phase separation regulates gene networks required for hNPC identity. These findings extend current understanding of ATRX function beyond its roles in chromatin structure and suggest that LLPS is a key regulatory mechanism by which ATRX supports neurodevelopment. This study opens avenues for further investigation into how dysregulation of ATRX and its phase-separation ability may contribute to the pathogenesis of ATR-X syndrome and related neurodevelopmental disorders.
